The aim of this project is to determine if sunscreens can fail to protect against UV damage by transferring absorbed UV energy to DNA. This project has three immediate goals (I) measure the interaction of sunscreen agents (e.g, octyl methoxycinnamate) with DNA through fluorescence and absorption spectroscopy; (ii) select the most favorable fluorescent DNA base analog- 2-aminopurine (2AP), or one of the pteridine-nucleoside analogs ("PNA's", M. Hawkins, Pediatric Branch, NCI)-to act as an energy acceptor from sunscreen; (iii) measure the efficiency of UV-excited energy transfer from active sunscreen agents to DNA and from DNA to sunscreen. In support of these goals, study of the dependence of energy transfer in DNA as a function of DNA length and conformation must continue. Sunscreens efficiently absorb UV radiation which can cause DNA damage in skin. The most favorable disposal mechanism for this absorbed energy is molecular internal conversion, leading to harmless heat dissipation. Studies of unfavorable energy-disposal mechanisms (e.g., radical and singlet oxygen formation) have been done to determine whether these processes, though rare, may contribute to DNA damage and the (bottom-line) failure of sunscreens to reduce the incidence of skin cancer in society. We will measure energy transfer, also an energy-dissipation mechanism, between sunscreen agents and DNA under in vitro conditions to determine the efficiency of transfer. Sunscreen agents can quickly be screened for unfavorable interaction with DNA, once protocols have been optimized. The next step would be to determine whether the in vitro interaction between sunscreen and DNA occurs in vivo. We have described 2AP-sensed base-to-base energy transfer in DNA in detail and, more recently, measured spectra of PNA-DNA from the Hawkins group. Neighboring bases (esp. adenine), base stacking, double helix formation and other DNA interactions cause spectroscopic changes that can be measured with commonly available absorption and fluorescence spectrophotometers. Spectral shift analysis (previously developed) as a function of temperature and solvent properties, as well as time-resolved fluorescence measurements will be performed to obtain native DNA spectroscopic signatures. Changes upon addition of sunscreen can then be precisely measured and the efficiency of energy transfer (or other interaction) determined (Xu and Nordlund, 2000). DNA damage would be directly proportional to this efficiency.